Introduction Sir Alexander Fleming discovered the first antibiotic, penicillin, in 1929. Development of penicillin was given high priority as part of the effort in World War II, and penicillin became widely used after the war. Resistant bacteria arose almost immediately. Not only are resistant bacteria still a problem with the penicillins, but they are a problem or potential problem with all antibiotics. Even daily newspapers and TV shows now carry stories about resistant bacteria. As a sales representative for antibiotics, you should understand bacterial resistance and how it affects physician treatment decisions.
[CALLOUT] Doctors are more concerned than ever about bacterial resistance to antibiotics. As a sales representative, you can expect to receive many questions about resistance.
Resistant pathogens can be a major problem. Consider Streptococcus
, for instance. When doctors first used penicillin widely in the 1940s,
pneumococcal isolates were extremely susceptible
to penicillin. Pneumonia
caused by S. pneumoniae
could be cured easily by quite small doses of
In the 1960s, S. pneumoniae
with intermediate susceptibility
began to be isolated in various parts of the world. In the 1970s, resistant
were isolated. Resistant strains of S. pneumoniae
amount to upwards of 45% of
isolates in some countries. Resistance can vary by geographic location. For
example, in the U.S. in 1991 and 1992, intermediately susceptible or resistant
strains were almost 7% of all strains nationwide, but 20% of the strains in Dallas,
Texas, were resistant. The magnitude of the potential problem in this country is
underscored by the estimated 5,000 cases of meningitis, 500,000 cases of
pneumonia, and 6 million cases of otitis media caused by S. pneumoniae
[CALLOUT] Doctors will be aware of specific problems with bacterial resistance to antibiotics in their practice area and hospitals. As a sales representative, you should also be aware of the local patterns of resistance.
strains that are of increasing
concern. Up to 30% of H. influenzae
strains produce beta-lactamase enzymes,
creating resistance to antibiotics that are beta-lactamase susceptible.2 In the
U.S., H. influenzae
accounts for 50% of cases of acute exacerbation of chronic
bronchitis,3 and 27% of cases of acute maxillary sinusitis.4
In selecting and using an antibiotic, the physician must keep in mind the problem
of resistance. It is important not only to avoid having resistant bacteria develop in
the patient being treated, but also to keep from increasing the prevalence of
resistant pathogens in the community. Resistance
has two different meanings in the context of infections:
· Host resistance: A host with a compromised immune system may be more
susceptible to infection than a normal person is. Infection arises when the host is unable to combat successfully the entry of a few bacterial pathogens, which can multiply and cause disease.
Some organs or tissues in a host may be susceptible to infection by a certain pathogen, while other organs or tissues in the same individual may be resistant to that pathogen. Some bacteria, S. pneumoniae
for instance, infect the lungs, causing pneumonia, more often than they infect other organs.
· Bacterial resistance: In this module, resistance refers to the relative
susceptibility of a pathogenic microorganism to an antibiotic. A pathogen that is not susceptible to a given antibiotic is said to be resistant to that antibiotic.
How antibiotics work
To understand the mechanisms of bacterial resistance to antibiotics, it will be
necessary to review four of the major actions of antibiotics.
Interference with synthesis of bacterial cell walls
Production of certain components of the bacterial cell wall is inhibited by the
penicillins and cephalosporins. These antibiotics are effective against
microorganisms that are multiplying, because they interfere with cell wall
. Without a cell wall, bacteria absorb water, swell, burst, and die.
Atypical bacteria without cell walls, like Mycoplasma pneumoniae
, are unaffected
by the penicillins and cephalosporins. The same is true of all animal and human
cells, for they do not have cell walls. Interference with protein synthesis
Bacteria contain ribosomes
, on which proteins are synthesized. Ribosomes
consist of 30S and 50S subunits. Antibiotics of the macrolide group bind to the
50S subunits of ribosomes and block protein synthesis
. Without new proteins,
bacteria cannot grow. Macrolides cannot bind to human ribosomes, which do not
have 50S subunits. Therefore, macrolides do not affect protein synthesis in the
human host. Because their action does not involve the cell wall, macrolides may
be effective against pathogens that lack cell walls, such as M. pneumoniae
against microorganisms that have developed resistance to penicillins or
cephalosporins. Interference with nucleic acid synthesis
Other classes of antibiotics, such as the quinolones (and fluoroquinolones),
interfere with synthesis of the bacterial chromosome
during division. In
particular, the quinolones interfere with the action of an enzyme, called DNA
gyrase. This enzyme uncoils bacterial DNA before the DNA is replicated, and
coils it again after replication. Human cells use a different mechanism for DNA
synthesis, so their cell division is not blocked by these antibiotics.
[CALLOUT] Some of the quinolones include Cipro® (Bayer Pharmaceutical), Floxin® (McNeil), and Noroxin® (Merck).
HEALTH HISTORY FORM AGE________BIRTHDATE_____________S.S.NO. ________________EMAIL ADDRESS__________________ RESIDENCE ADDRESS______________________________________ HOME PHONE____________________ ______________________________________ CELL PHONE_____________________ EMPLOYED BY___________________________________________ BUS. PHONE_____________________ PRESENT POSITION_______________________
THE TIME CODE SHOW curated by Fabiola Naldi and Alessandra Pioselli 3rd July – 17th August 2008 Opening: Thursday, July 3rd 2008, 6.30 p.m. The inauguration of THE TIME CODE SHOW – curated by Fabiola Naldi and Alessandra Piosel i, and conceived as a “choral” moment which retraces the stages of the TIME CODE project – wil be held on July 3, at MAMbo – the Museum of Modern Art